Hydrogen bond

About: Hydrogen bond is a research topic. Over the lifetime, 57701 publications have been published within this topic receiving 1306326 citations.

A DFT Study on Intramolecular Hydrogen Bonding in 2-Substituted Phenols: Conformations, Enthalpies, and Correlation with Solute Parameters

Abstract: For a series of 61 2-substituted phenols, 2-X−PhOH, forming a total of 73 intramolecular hydrogen bonds, the intramolecular hydrogen bond enthalpy, ΔHintra-HB, has been determined by density functional theory (DFT) calculations on the B3LYP/6-31G(d,p)//B3LYP/6-31G(d,p) level. The ΔHintra-HB was defined as the enthalpy difference between the hydrogen-bonded (HB) form and the lowest-energy conformer in which the OH is rotated into the “away” position. The correlation of ΔHintra-HB with geometrical factors such as r(O−H), or r(OH···A), with A as the hydrogen bond accepting atom, was generally very poor, showing that none of these parameters can be used as an universal descriptor for the hydrogen bond strength. The relation between ΔHintra-HB and ν(O−H) intra-HB is also insignificant, in contrast with previous estimates. The data clearly demonstrate that the genuine ΔHintra-HB of a phenolic compound cannot be unequivocally derived by simple rotation of the OH group into the “away” orientation, because additio...

Slow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues.

Abstract: The modes of binding to thermolysin of two phosphonamidate peptide inhibitors, carbobenzoxy-GlyP-L-Leu-L-Leu (ZGPLL) and carbobenzoxy-L-PheP-L-Leu-L-Ala (ZFPLA), have been determined by X-ray crystallography and refined at high resolution to crystallographic R-values of 17.7% and 17.0%, respectively. (GlyP is used to indicate that the trigonal carbon of the peptide linkage is replaced by the tetrahedral phosphorus of a phosphonamidate group.). These inhibitors were designed to be structural analogues of the presumed catalytic transition state and are potent inhibitors of thermolysin (ZGPLL, Ki = 9.1 nM; ZFPLA, Ki = 0.068 nM) [Bartlett, P. A., & Marlowe, C. K. (1987) Biochemistry (following paper in this issue)]. ZFPLA binds to thermolysin in the manner expected for the transition state and, for the first time, provides direct support for the presumed mode of binding of extended substrates in the S2 subsite. The mode of binding of ZFPLA displays all the interactions that are presumed to stabilize the transition state and supports the postulated mechanism of catalysis [Hangauer, D. G., Monzingo, A. F., & Matthews, B. W. (1984) Biochemistry 23, 5730-5741]. The two oxygens of the phosphonamidate moiety are liganded to the zinc to give overall pentacoordination of the metal. For the second inhibitor the situation is different. Although both ZFPLA and ZGPLL have similar modes of binding in the S1' and S2' subsites, the configurations of the carbobenzoxy-Phe and carbobenzoxy-Gly moieties are different. For ZFPLA the carbonyl group of the carbobenzoxy group is hydrogen bonded directly to the enzyme, whereas in ZGPLL the carbonyl group is rotated 117 degrees, and there is a water molecule interposed between the inhibitor and the enzyme. For ZGPLL only one of the phosphonamidate oxygens is liganded to the zinc. Correlated with the change in inhibitor-zinc ligation from monodentate in ZGPLL to bidentate in ZFPLA there is an increase in the phosphorus-nitrogen bond length of about 0.25 A, strongly suggesting that the phosphonamide nitrogen in ZFPLA is cationic, analogous to the doubly protonated nitrogen of the transition state. The observation that the nitrogen of ZFPLA appears to donate two hydrogen bonds to the protein also indicates that it is cationic. The different configurations adopted by the respective inhibitors are correlated with large differences in their kinetics of binding [Bartlett, P. A., & Marlowe, C. K. (1987) Biochemistry (following paper in this issue)]. These differences in kinetics are not associated with any significant conformational change on the part of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and Structural Characterization of Helix-Forming β-Peptides: trans-2-Aminocyclopentanecarboxylic Acid Oligomers

Abstract: Synthetic protocols and circular dichroism (CD) spectra are reported for a series of oligomers of (R,R)-trans-2-aminocyclopentanecarboxylic acid (trans-ACPC). The two longest oligomers, a hexamer and an octamer, have also been examined crystallographically. Both crystal structures show that the β-peptide backbone adopts a regular helix that is defined by a series of interwoven 12-membered ring hydrogen bonds (“12-helix”). Each hydrogen bond links a carbonyl oxygen to an amide proton three residues toward the C-terminus. CD data suggest that the conformational preference of trans-ACPC oligomers in methanol is strongly length-dependent, which implies that 12-helix formation is a cooperative process, as seen for the α-helix formed by conventional peptides. Previous work has established that oligomers and polymers of β-amino acids can adopt helical conformations, but the 12-helix is an unprecedented β-peptide secondary structure.

Partitioning of free energy contributions in the estimation of binding constants : Residual motions and consequences for amide-amide hydrogen bond strengths

Abstract: Any bimolecular association is entropically unfavorable because of degrees of freedom of translation and rotation lost when two molecules come together to form a complex. For a ligand of molecular weight 200, the formation of a «rigid» dimer (one in which there is no residual relative motion of the associating components A and B in the complex A.B) opposes binding by ca. 10 -9 to 10 -10 M -1 in binding constant